Bicyclic heteroarylaminoalkyl phenyl derivatives as PI3K inhibitors

Abstract

This application relates to derivatives of Formula I: and pharmaceutically acceptable salts thereof, which are inhibitors of PI3K, and compositions and methods of treatment related thereto.

What is claimed is: 
     
       1. A pharmaceutical composition comprising a compound selected from:
 4-{3-chloro-6-ethoxy-2-fluoro-5-[1-([1,3]thiazolo[5,4-d]pyrimidin-7-ylamino)ethyl]phenyl}pyrrolidin-2-one; 
 4-{3-chloro-6-ethoxy-2-fluoro-5-[1-(pyrido[3,2-d]pyrimidin-4-ylamino)ethyl]phenyl}pyrrolidin-2-one; 
 5-{3-chloro-6-methoxy-2-methyl-5-[(1S)-1-(pyrido[3,2-d]pyrimidin-4-ylamino)ethyl]phenyl}-N,N-dimethylpyridine-2-carboxamide; and 
 4-chloro-N-ethyl-3′,5′-difluoro-3-methyl-6-[1-(pyrido[3,2-d]pyrimidin-4-ylamino)ethyl]biphenyl-2-carboxamide; 
 
       or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier. 
     
     
       2. The pharmaceutical composition of  claim 1 , wherein the compound is selected from:
 (S)-4-(3-chloro-6-ethoxy-2-fluoro-5-((S)-1-(pyrido[3,2-d]pyrimidin-4-yl amino)ethyl)phenyl)pyrrolidin-2-one; 
 (R)-4-(3-chloro-6-ethoxy-2-fluoro-5-((R)-1-(pyrido[3,2-d] pyri mi di n-4-ylamino)ethyl)phenyl)pyrrolidin-2-one; 
 (S)-4-(3-chloro-6-ethoxy-2-fluoro-5-((R)-1-(pyrido[3,2-d]pyrimidin-4-ylamino)ethyl)phenyl)pyrrolidin-2-one; and 
 (R)-4-(3-chloro-6-ethoxy-2-fluoro-5-((S)-1-(pyrido[3,2-d]pyrimidin-4-ylamino)ethyl)phenyl)pyrrolidin-2-one; 
 or a pharmaceutically acceptable salt thereof. 
 
     
     
       3. The pharmaceutical composition of  claim 1 , wherein the compound is 4-{3-chloro-6-ethoxy-2-fluoro-5-[1-(pyrido[3,2-d]pyrimidin-4-ylamino)ethyl]phenyl}pyrrolidin-2-one, or a pharmaceutically acceptable salt thereof. 
     
     
       4. The pharmaceutical composition of  claim 3 , wherein the compound is (S)-4-(3-chloro-6-ethoxy-2-fluoro-5-((S)-1-(pyri do[3,2-d]pyrimidin-4-ylamino)ethyl)phenyl)pyrrolidin-2-one, or a pharmaceutically acceptable salt thereof. 
     
     
       5. The pharmaceutical composition of  claim 3 , wherein the compound is (R)-4-(3-chloro-6-ethoxy-2-fluoro-5-((R)-1-(pyri do[3,2-d]pyrimidin-4-ylamino)ethyl)phenyl)pyrrolidin-2-one, or a pharmaceutically acceptable salt thereof. 
     
     
       6. The pharmaceutical composition of  claim 3 , wherein the compound is (S)-4-(3-chloro-6-ethoxy-2-fluoro-5-((R)-1-(pyri do[3,2-d]pyrimidin-4-ylamino)ethyl)phenyl)pyrrolidin-2-one, or a pharmaceutically acceptable salt thereof. 
     
     
       7. The pharmaceutical composition of  claim 3 , wherein the compound is (R)-4-(3-chloro-6-ethoxy-2-fluoro-5-((S)-1-(pyri do[3,2-d]pyrimidin-4-ylamino)ethyl)phenyl)pyrrolidin-2-one, or a pharmaceutically acceptable salt thereof. 
     
     
       8. A compound, which is 4-{3-chloro-6-ethoxy-2-fluoro-5-[1-(pyrido[3,2-d]pyrimidin-4-ylamino)ethyl]phenyl}pyrrolidin-2-one, or a pharmaceutically acceptable salt thereof. 
     
     
       9. The compound of  claim 8 , wherein the compound is (S)-4-(3-chloro-6-ethoxy-2-fluoro-5-((S)-1-(pyrido[3,2-d]pyrimidin-4-ylamino)ethyl)phenyl)pyrrolidin-2-one, or a pharmaceutically acceptable salt thereof. 
     
     
       10. The compound of  claim 8 , wherein the compound is (R)-4-(3-chloro-6-ethoxy-2-fluoro-5-((R)-1-(pyrido[3,2-d]pyrimidin-4-ylamino)ethyl)phenyl)pyrrolidin-2-one, or a pharmaceutically acceptable salt thereof. 
     
     
       11. The compound of  claim 8 , wherein the compound is (S)-4-(3-chloro-6-ethoxy-2-fluoro-5-((R)-1-(pyrido[3,2-d]pyrimidin-4-ylamino)ethyl)phenyl)pyrrolidin-2-one, or a pharmaceutically acceptable salt thereof. 
     
     
       12. The compound of  claim 8 , wherein the compound is (R)-4-(3-chloro-6-ethoxy-2-fluoro-5-((S)-1-(pyrido[3,2-d]pyrimidin-4-ylamino)ethyl)phenyl)pyrrolidin-2-one, or a pharmaceutically acceptable salt thereof.